Morne Steyn and Jean de Villiers touched down as a second-half South African barrage broke England's resistance and helped them secure a 22-17 win in the first Test in Durban.
England met the Springboks challenge head on at Kings Park and were level at 6-6 at half-time after Owen Farrell and Steyn traded penalties.
South Africa began to gain the upper hand after the break as Steyn and captain De Villiers broke through, and the hosts held on despite two more Farrell penalties and a late Ben Foden consolation try.
England were handed the chance to open the scoring when Eben Etzebeth, one of three debutants for the hosts, was penalised. Farrell drilled a long-range effort between the posts and the fly-half had an opportunity to open up the Springboks defence soon after but his delicate kick was not read by any team-mates.
South Africa pulled themselves level with a Steyn penalty after Ben Youngs, who was given a thorough examination throughout, lost possession and England were caught offside.
The tourists relieved the pressure when a South African offside allowed Farrell another shot at goal. But it was a penalty soon cancelled out by Steyn after another offside decision.
England carried their fighting spirit into the second half but it was South Africa who took a grip on the game by claiming the opening try in the 48th minute. Prop Jannie du Plessis and De Villiers were both stopped inches short of the line before the ball was spun out left for Steyn to crash over.
South Africa continued to pour forward with Bryan Habana proving a particularly tricky customer. Eventually England had to crack and it was De Villiers who broke through for a second try on the hour as he raced onto a JP Pietersen pass and powered over the line.
A kick over the top by Farrell looked to have proved fruitless but England came away with a penalty and the fly-half reduced the arrears to 16-9. Farrell then cut that by another three points with just under 15 minutes remaining after another South African indiscretion.
The Springboks regrouped and extended their lead a little further when an England offside presented Steyn with a kickable penalty, and he added another in the closing moments before the visitors claimed a consolation when Foden dived over in the corner.